Duke MHCRC investigators have made major contributions to knowledge of late life depression over the past 10 years, with recruitment of epidemiologic, clinical, psychosocial, biological psychiatry and basic science investigators. Through its Cores, data base and educational efforts, the MHCRC has provided essential support to a wide range of productive associated investigators and trainees. This enabling, research multiplier role of the Center will continue. The Center provides unique resources in epidemiology, recruitment, assessment, research consultation, statistics, clinical biology, pharmacology, molecular biology and research training. Five distinct Cores are organized: administrative-educational; recruitment-assessment; statistics-data management; brain imaging; and preclinical. New structural features are: a research clinic for an intensive, multidisciplinary study of course; inclusion of the public mental health sector; a reorganized Preclinical Core; and a Blood Sample Bank to facilitate future pilot studies. The MHCRC also has the scientific aim of integrating disciplines relevant to late life depression, a goal beyond the logistic capability of individual projects. Based on our scientific achievements to date, we now propose to test specific hypotheses in a multifactorial model of risk factors for adverse course in late life depression. The major factors are psychosocial, brain structural change, and neuroendocrine dysfunction, with medical illness and clinical features as important covariates. Other major scientific emphases are: a) comparison of early and late onset elderly depression; b) preclinical modelling of geriatric depression in the aging rat; c) coordinated functional and cell biology studies of the serotonin transporter and glucocorticoids in depression and in the animal model; d) pilot studies of molecular genetics of the serotonin transporter and other candidate genes.